PHARMACOKINETICS OF (+ -)-4-DIETHYLAMINO-1,1-DIMETHYLBUT-2-YN-1-YL 2-CYCLOHEXYL-2-HYDROXY-2-PHENYLACETATE MONOHYDROCHLORIDE MONOHYDRATE - 1ST COMMUNICATION - ABSORPTION, DISTRIBUTION AND EXCRETION AFTER SINGLEADMINISTRATION OF C-14-LABELED COMPOUND TO RATS AND DOGS/

The absorption, distribution and excretion of radioactivity were studi ed in rats and dogs after intravenous or oral administration of NS-21 ((+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy -2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4). C-14 -NS-21 was rapidly absorbed from the gastrointestinal tract after oral administration to rats and dogs. NS-21 was absorbed throughout the wh ole area of the small intestine. NS-21 entered the systemic circulatio n via the portal vein because the transfer of radioactivity into the l ymph was negligible. The presence of food did not affect the absorptio n ratio of NS-21. There was no difference in the plasma concentrations of radioactivity after intravenous and oral administrations of C-14-N S-21 to male and female rats. After oral administration of 3, 30 or 10 0 mg/kg of C-14-NS-21 to rats, the area under the plasma concentration -time curve increased in a dose-dependent manner. After oral administr ation of C-14-NS-21 to rats, radioactivity was distributed throughout the whole body. The concentrations of radioactivity in most tissues re ached their maximums within 2 h, and then declined as the plasma conce ntration decreased. No radioactivity was detected in most tissues 168 h after administration. In vitro serum binding of C-14-NS-21 was more than 98 % in all the animal species tested. NS-21 bound to both human serum albumin and alpha(1)-acid glycoprotein. Radioactivity was mainly excreted into the feces via bile in rats, and evenly excreted into th e urine and feces in dogs. No differences were observed in the excreti on of radioactivity between male and female rats.